Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
ASTRAL-4
A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed-Dose Combination in Subjects With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
1 other identifier
interventional
268
2 countries
50
Brief Summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) with and without ribavirin (RBV) for 12 weeks and SOF/VEL FDC for 24 weeks in adults with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) class B cirrhosis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2014
Shorter than P25 for phase_3
50 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2014
CompletedFirst Submitted
Initial submission to the registry
July 24, 2014
CompletedFirst Posted
Study publicly available on registry
July 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2015
CompletedResults Posted
Study results publicly available
December 14, 2016
CompletedNovember 15, 2018
October 1, 2016
1.1 years
July 24, 2014
August 24, 2016
October 19, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Up to 24 weeks plus 30 days
Secondary Outcomes (6)
Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Posttreatment Weeks 4 and 24
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Percentage of Participants With Virologic Failure
Up to Posttreatment Week 24
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score
Baseline to Posttreatment Week 24
- +1 more secondary outcomes
Study Arms (3)
SOF/VEL 12 weeks
EXPERIMENTALParticipants will receive SOF/VEL FDC for 12 weeks.
SOF/VEL+RBV 12 weeks
EXPERIMENTALParticipants will receive SOF/VEL FDC plus RBV for 12 weeks.
SOF/VEL 24 weeks
EXPERIMENTALParticipants will receive SOF/VEL FDC for 24 weeks.
Interventions
400/100 mg tablets administered orally once daily
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Eligibility Criteria
You may qualify if:
- Willing and able to provide written informed consent
- HCV RNA \> 10\^4 IU/mL at screening
- Chronic HCV infection (≥ 6 months)
- Confirmed CPT class B (7-9) at screening
You may not qualify if:
- Current or prior history of solid organ transplantation, significant pulmonary disease, significant cardiac disease, or porphyria
- Inability to exclude hepatocellular carcinoma (HCC) by imaging within 6 months of baseline/Day 1
- Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
- Screening ECG with clinically significant abnormalities
- Prior exposure to SOF or any other nucleotide analogue HCV nonstructural protein 5B (NS5B) inhibitor or any HCV NS5A inhibitor
- Laboratory results outside of acceptable ranges at screening
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (50)
Unknown Facility
Phoenix, Arizona, United States
Unknown Facility
La Jolla, California, United States
Unknown Facility
Los Angeles, California, 90048, United States
Unknown Facility
Los Angeles, California, United States
Unknown Facility
Pasadena, California, United States
Unknown Facility
San Francisco, California, United States
Unknown Facility
Aurora, Colorado, United States
Unknown Facility
Washington D.C., District of Columbia, United States
Unknown Facility
Gainesville, Florida, United States
Unknown Facility
Jacksonville, Florida, 32256, United States
Unknown Facility
Miami, Florida, United States
Unknown Facility
Tampa, Florida, United States
Unknown Facility
Marietta, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Indianapolis, Indiana, 46202, United States
Unknown Facility
Indianapolis, Indiana, 46237, United States
Unknown Facility
Kansas City, Kansas, United States
Unknown Facility
Monroe, Louisiana, 71280, United States
Unknown Facility
New Orleans, Louisiana, United States
Unknown Facility
Baltimore, Maryland, United States
Unknown Facility
Boston, Massachusetts, United States
Unknown Facility
Ann Arbor, Michigan, United States
Unknown Facility
Detroit, Michigan, United States
Unknown Facility
Rochester, Minnesota, United States
Unknown Facility
Jackson, Mississippi, United States
Unknown Facility
St Louis, Missouri, United States
Unknown Facility
Santa Fe, New Mexico, 87505, United States
Unknown Facility
New York, New York, 10016, United States
Unknown Facility
New York, New York, 10029, United States
Unknown Facility
New York, New York, 10032, United States
Unknown Facility
Chapel Hill, North Carolina, United States
Unknown Facility
Charlotte, North Carolina, 28204, United States
Unknown Facility
Durham, North Carolina, United States
Unknown Facility
Cleveland, Ohio, 44195, United States
Unknown Facility
Cleveland, Ohio, United States
Unknown Facility
Philadelphia, Pennsylvania, 19104, United States
Unknown Facility
Philadelphia, Pennsylvania, 19107, United States
Unknown Facility
Pittsburgh, Pennsylvania, United States
Unknown Facility
Providence, Rhode Island, 02905, United States
Unknown Facility
Germantown, Tennessee, 38138, United States
Unknown Facility
Nashville, Tennessee, 37211, United States
Unknown Facility
Arlington, Texas, 76012, United States
Unknown Facility
Dallas, Texas, United States
Unknown Facility
San Antonio, Texas, United States
Unknown Facility
Murray, Utah, United States
Unknown Facility
Fairfax, Virginia, United States
Unknown Facility
Norfolk, Virginia, 23502, United States
Unknown Facility
Richmond, Virginia, United States
Unknown Facility
Seattle, Washington, United States
Unknown Facility
San Juan, 00927, Puerto Rico
Related Publications (5)
Charlton MR, O'Leary JG, Bzowej NH, Muir AJ, Korenblat KM, Fenkel JM, et al. Sofosbuvir/Velapatasvir Fixed Dose Combination for the Treatment of HCV in Patients with Decompensated Liver Disease: The Phase 3 ASTRAL-4 Study. Hepatology 2015; 62 (6): 1387A-1388A.
BACKGROUNDCurry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16.
PMID: 26569658RESULTAsselah T, Charlton M, Feld J, Foster GR, McNally J, Brainard DM, et al. The ASTRAL Studies: Evaluation of SOF/GS-5816 Single-Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection [Poster P1332]. J Hepatol 2015; 62:S855-S6.
RESULTYounossi ZM, Stepanova M, Charlton M, Curry MP, O'Leary JG, Brown RS, Hunt S. Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial. Lancet Gastroenterol Hepatol. 2016 Oct;1(2):122-132. doi: 10.1016/S2468-1253(16)30009-7. Epub 2016 Aug 3.
PMID: 28404069DERIVEDYounossi ZM, Stepanova M, Feld J, Zeuzem S, Sulkowski M, Foster GR, Mangia A, Charlton M, O'Leary JG, Curry MP, Nader F, Henry L, Hunt S. Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2017 Mar;15(3):421-430.e6. doi: 10.1016/j.cgh.2016.10.037. Epub 2016 Nov 12.
PMID: 27847279DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
There were no limitations affecting the analysis or results.
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Anu M Osinusi, MD, MPH
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 24, 2014
First Posted
July 28, 2014
Study Start
July 1, 2014
Primary Completion
August 1, 2015
Study Completion
November 1, 2015
Last Updated
November 15, 2018
Results First Posted
December 14, 2016
Record last verified: 2016-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 18 months after study completion
- Access Criteria
- A secured external environment with username, password, and RSA code.
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.